Anthrax is a well-known infectious disease caused by a Gram-positive bacterium, Bacillus anthracis (B. anthracis). Among the three types of anthrax infection (cutaneous, gastrointestinal, and inhalation), cutaneous anthrax is the most common and is relatively easily treatable with various antibiotics. The other two types of anthrax infections are rare, but usually fatal even with aggressive anti-microbial therapy.
The major virulence factor, anthrax toxin, is composed of three proteins: protective antigen (PA, 83 kilo Dalton, kDa), edema factor (EF, 89 kDa), and lethal factor (LF, 90 kDa). The toxin components act in the binary combinations of PA+EF (edema toxin), and PA+LF (lethal toxin). PA is a cell receptor-binding protein and delivers the other two proteins (EF and LF) into the cytosol of infected cells.
The most effective known method for preventing anthrax is vaccination. The current and only FDA-approved anthrax vaccine in the United States (produced by Emergent BioSolutions Inc. under the trademark BioThrax® Anthrax Vaccine Adsorbed) is produced from a sterile cell-free filtrate from an avirulent B. anthracis V770-NP1-R strain. The licensed anthrax vaccine is also called Anthrax Vaccine Adsorbed (or AVA). The vaccine primarily consists of PA, and aluminum hydroxide is used as an adjuvant. The vaccine was developed during the 1950s and 1960s and is licensed by the FDA to Emergent BioSolutions Inc. The vaccine is safe, showing less than 0.06% systemic reactions. The ability of the vaccine to elicit an immune response in humans is well-documented. The BioThrax® Anthrax Vaccine Adsorbed vaccine is currently licensed for six doses over 18 months followed by annual boosts.
Although the BioThrax® Anthrax Vaccine Adsorbed vaccine is effective and safe, new immunogenic compositions for preparing a vaccine that protects a subject against a lethal B. anthracis infection using recombinant technologies are under development. Recombinant vaccine protein components could allow the use of new types of adjuvants that could elicit enhanced or more diverse immune responses. Because protective antigen (PA) is the common factor required for both the actions of LF and EF, it is often used to prepare vaccines for anthrax. Recombinant PA (rPA), however, does not elicit a strong protective response against the disease and there have also been issues with its stability. For example, the FDA in November 2006 placed a clinical trial using VaxGen's rPA102 vaccine on hold because of stability issues with the vaccine formulation. Accordingly, there is a need for a rPA anthrax vaccine that has improved stability.